Critical U.S. drug shortage worsening

By Christopher K. Hepp, Inquirer Staff Writer

Posted: December 12, 2010

The nation is facing an unprecedented drug shortage.

From cancer treatments to surgical sedatives to standard emergency-room remedies, the pharmaceutical supply cabinet is increasingly bare of the drugs of choice, according to doctors, advocacy groups, and the FDA.

Industry consolidation, random and unpredictable manufacturing problems, and simple economics, they say, have conspired to narrow the pipeline that delivers needed drugs to the point where shortfalls of key medications are more frequent and prolonged.

As a result, physicians must use second- and third-tier treatments. In some instances, according to a survey of 1,800 doctors and pharmacists by the Institute for Safe Medical Practices, patients have died for want of the preferred drug therapy.

And, in an ironic twist, the shortage of sedating drugs used in executions forced a number of states this year to put the death penalty temporarily on hold.

"It is a serious and growing problem," said John Hansen-Flaschen, chief of the Pulmonary, Allergy & Critical Care Division at the University of Pennsylvania Hospital. "For 12 or 18 months now, we have had sustained, absolute shortages of some of the most common intravenous drugs used in patient medicine."

Those include intravenous Lasix, a diuretic commonly used to treat congestive heart failure, and Cisatracurium, a muscle relaxant used in surgery, he said.

Elsewhere, there are critical shortages of chemotherapy drugs and even morphine, according to the American Society of Clinical Oncology (ASCO).

The American Society of Anesthesiologists (ASA) reports that its practitioners have been severely hampered by shortages of a variety of drugs used to sedate and immobilize patients undergoing surgery, including propofol, which is also used in executions.

"It has gotten to the point where anesthesiologists are thinking about it as they drive to work: Do I have a shortage of any these drugs? . . . How will I work around it?" said Mark Warner, a physician and president of the ASA.

Almost all the shortages are generic drugs, Hansen-Flaschen said, an apparent reflection of the fact that there are fewer manufacturers of such medications, which generate less profit than do brand-name drugs. With few producers, any breakdown in manufacturing or shortage of raw materials can trigger widespread shortages.

"This is more than just an inconvenience for hospitals or the clinicians," said Cynthia Reilly, director of practice development for the American Society of Health-System Pharmacists. "It is really affecting patient safety."

According to Erin Fox, program director of the University of Utah's Drug Information Service, the current list of shortages is the most the agency has seen in a decade of tracking the issue. As of Dec. 1, there had been shortages of 199 drugs, she said, two more than all of last year, the previous high.

Anecdotally, others say, the situation is the most acute it has been in more than a generation.

"This is probably the worst drug shortage in more than 30 years," said physician Michael Link, president-elect of the American Society of Clinical Oncology.

The society was among four advocacy groups - including the pharmacists, the anesthesiologists, and the medical-practices institute - to lead a summit on the issue last month in Bethesda, Md. The groups are now putting together a formal list of recommendations for the Food and Drug Administration and the pharmaceutical industry.

Earlier this month, responding to a shortage of chemotherapy drugs in Minnesota, Sen. Amy Klobuchar (D., Minn.) wrote to FDA Commissioner Margaret Hamburg asking that the FDA intervene to "ensure that patients have access to the medications that are essential to their health and well-being."

As it is, the FDA has few tools to resolve shortages. It cannot, for instance, order drug companies to make more drugs.

It will accelerate approval processes in situations of shortages, according to Valerie Jensen, a project manager with the FDA's Drug-Shortage Unit. It has also cleared for use nonlicensed drugs from overseas that are similar to the medications that are scarce.

"It is a systemic problem" with no easy solution, said Warner, of the ASA. "There are a number of steps along the way that can be improved, such as making sure we communicate better, making sure that if there is going to be a shortage that the pharmaceutical manufacturers let the FDA know early and the FDA lets the providers know as early as possible."

Hospira Inc., a manufacturer of generic drugs that produces many of the drugs now in short supply, issued a statement last week making it clear that it has heard the message.

"Hospira shares the medical community's concerns about current drug shortages, and we are doing everything we can to meet customer needs," the company said. "We know that the biggest challenge customers and clinicians are facing is communication, and we are taking strides to improve communication about shortages."

Much of the problem seems to reside among generic medications, particularly sterile injectable drugs, such as Lasix and epinephrine, which is used to treat heart attacks and patients with allergic reactions.

"This year, over 70 percent of our shortages are sterile injectables," Jensen said. "We are looking at why that is occurring."

Most likely it is a combination of reasons, she said, including industry consolidation, which means fewer generic manufacturers and the production of a broader but shallower array of drugs.

Sterile injectables are difficult and costly to make, she said. Often, cost factors contribute to a decision by a manufacturer to stop making a medication, she said.

"We often hear it was a business decision," Jensen said.

In May, for instance, drugmaker Teva Pharmaceutical Industries Ltd., an Israeli firm with U.S. headquarters in North Wales, announced it would stop making propofol because the drug is hard to manufacture and produces little or no profit. The drug was already in short supply at the time.

The shortage of propofol as well as a second sedative used in executions, sodium thiopental, left a number of states, including Ohio and Arizona, scrambling for drugs to carry out the death penalty. Executions in Oklahoma and Kentucky were delayed.

Richard F. Demers is the director of pharmacy services for the University of Pennsylvania Hospital. It falls to him to find replacement drugs when a shortage hits.

"You scramble," he said. "You look at all the legitimate sources of distribution you can find. You go through your list of alternative products and get those products lined up. And you have to do a lot of reeducation of physicians and nurses on the spot."

Demers said he was particularly troubled that the number of shortages has been rising over time. "I have two concerns: Why has this become a trend, and where is it going?"

In the short run, he suggested, as others have, that simply more warning time could mitigate some of the damage.

"There is a good two to three months of supply in the supply chain," he said. "Typically, we don't learn of a shortage until we order a drug from distributors, and they don't have any and can't get it.

"Drugmakers need to remember that this is more than a distribution or manufacturing business. At the end of all this is somebody who is really very sick and very dependent on these drugs. I'm not sure the folks in the [management] c-suites of these companies get that."